Preliminary amino acid sequence information on the H-2K and H-2D transplantation antigens of the mouse and their human counterparts has left a number of key questions unanswered regarding the origin, function, and evolutionary interrelationships of these molecules. We wish to identify evolutionary precursors or successors of these molecules and determine whether the molecules possess obvious functional regions such as the hypervariable and conserved regions of immunoglobulin molecules. We wish to know when the mouse transplantation antigens diverged from one another and from their human counterparts. The above questions will be approached through the microsequence analysis of the molecules using exciting new instrument systems now operational in our laboratories. We propose to examine the amino acid sequences of the selected H-2K and H-2D gene products and of other relevant cell surface molecules.